@article{a867479cae66493d9b41f5187d2bdfda,
title = "Dopamine neuron activity encodes the length of upcoming contralateral movement sequences",
abstract = "Dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement speed, and loss of these neurons leads to bradykinesia in Parkinson's disease (PD). However, other aspects of movement vigor are also affected in PD; for example, movement sequences are typically shorter. However, the relationship between the activity of DANs and the length of movement sequences is unknown. We imaged activity of SNc DANs in mice trained in a freely moving operant task, which relies on individual forelimb sequences. We uncovered a similar proportion of SNc DANs increasing their activity before either ipsilateral or contralateral sequences. However, the magnitude of this activity was higher for contralateral actions and was related to contralateral but not ipsilateral sequence length. In contrast, the activity of reward-modulated DANs, largely distinct from those modulated by movement, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not ipsilateral, sequence length. These results indicate that movement-initiation DANs encode more than a general motivation signal and invigorate aspects of contralateral movements.",
keywords = "dopamine, laterality, length, movement, Parkinson's disease, substantia nigra pars compacta, vigor",
author = "Mendon{\c c}a, {Marcelo D.} and {da Silva}, {Joaquim Alves} and Hernandez, {Ledia F.} and Ivan Castela and Jos{\'e} Obeso and Costa, {Rui M.}",
note = "Funding Information: We thank Ana Vaz and Catarina Carvalho for mouse colony management, Thomas Akam and H{\'e}lio Rodrigues for help in behavioral box development and implementation, and the Champalimaud Hardware Platform (Filipe Carvalho, Artur Silva, and D{\'a}rio Bento) for support in the development of the behavioral hardware setup. We thank Cristina Alc{\'a}cer and Nuno Loureiro for their contributions during the 6-OHDA experiments. This work was supported by Funda{\c c}{\~a}o Para a Ci{\^e}ncia e Tecnologia (FCT) through a doctoral fellowship ( SFRH/BD/119623/2016 to M.D.M.) and Funda{\c c}{\~a}o Luso-Americana para o Desenvolvimento (FLAD) by a visiting student fellowship ( 2018/31 to M.D.M.); by a doctoral fellowship from the Gulbenkian Foundation (to J.A.d.S.), a Marie Curie Fellowship ( MSCA-IF-RI 2016 to L.F.H.), and a Spanish Ministry of Innovation and Sciences doctoral fellowship ( BES-2016-077493 to I.C.); and by ERA-NET , ERC ( COG 617142 ), HHMI ( IEC 55007415 ), National Institutes of Health ( 5U19NS104649 ), and the Simons-Emory International Consortium on Motor Control and the Aligning Science Across Parkinson{\textquoteright}s ( ASAP-020551 ) through the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research (MJFF) to R.M.C. Further support was obtained from the research infrastructure Congento, co-funded by Lisboa2020 and FCT ( LISBOA-01-0145-FEDER-022170 ). Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2024",
month = mar,
day = "11",
doi = "10.1016/j.cub.2024.01.067",
language = "English",
volume = "34",
pages = "1034--1047.e4",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "5",
}